Geographic Atrophy (GA)

Understanding Geographic Atrophy

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible vision loss.¹ Early or intermediate AMD may progress to the advanced forms, which include neovascular AMD (“wet” AMD) or GA (“dry” AMD),² and the risk of developing AMD increases with age.

AMD is the leading cause of permanent vision loss in people over the age of 65 in developed countries.³ Based on published studies, approximately one million people have GA in the United States and five million people have GA globally.^4,5

While there are multiple effective treatments available for wet AMD, there are currently no approved treatments for GA.

In people with GA, photoreceptors, which are light sensitive cells, deteriorate in the macula, a central portion of the retina responsible for central vision and color perception.⁶ This damage starts as small spots that grow into larger patches. As the cells in the macula die, the person starts to lose vision.⁶

A person with early AMD may notice problems with reading or night vision.⁷ Eventually, if the disease progresses to advanced stages, permanent blind spots (scotomas) in the center of the visual field will develop.

The cause of GA is thought to be multifactorial, with numerous environmental and genetic risk factors. The dysregulation of the complement cascade, an important part of the body’s immune system, plays a pivotal role.⁷

Excessive activation of the complement cascade results in destruction of healthy cells, which can lead to the onset or progression of many diseases including GA.^8,9

Pegcetacoplan (APL-2) in GA

Pegcetacoplan is a targeted C3 inhibitor designed to regulate uncontrolled or excessive complement activation. We believe that pegcetacoplan may slow the growth of GA lesions by regulating excessive complement activation.

Resources

• Macular Degeneration Association
• American Foundation for the Blind
• American Macular Degeneration Foundation
• American Academy of Ophthalmology Eye Health Organization
• Retina International
• Fighting Blindness Canada
• Macular Society
• Royal National Institute of Blind People (RNIB)

References

1. Fleckenstein M, Mitchell P, Freund KB, et al. The progression of geographic atrophy secondary to age-related macular degeneration. Ophthalmology 125.3 (2018):369-390. https://www.ncbi.nlm.nih.gov/pubmed/29110945. Accessed November 21, 2019.
2. Waugh N, Loveman E, Colquitt J, et al. Treatments for dry age-related macular degeneration and Stargardt disease: a systematic review. Southampton (UK): NIHR Journals Library; 2018 May. (Health Technology Assessment, No. 22.27.) Chapter 1, Introduction to age-related macular degeneration. Available from: https://www.ncbi.nlm.nih.gov/books/NBK500483/
3. Age-related macular degeneration. National Eye Institute Web site. 2018; https://nei.nih.gov/health/maculardegen/. Accessed November 21, 2019.
4. Tufail A, et al. Objective measurement of reading speed and correlation with patient-reported functional reading independence. Presented at the 15th EURETINA Congress, Nice, France, September 17-20, 2015. Accessed November 21, 2019.
5. The Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122:564-572.
6. Danis RP, Lavine JA, Domalpally A. Geographic atrophy in patients with advanced dry age-related macular degeneration: current challenges and future prospects. Clin Ophthalmol. 2015;9:2159–2174. Published 2015 Nov 20. doi:10.2147/OPTH.S92359
7. Murphy K, Weaver C. Innate immunity: the first lines of defense. In: Janeway's Immunobiology. 9th ed. London, UK: Garland Science; 2016.
8. Morgan P, et al. Complement, a target for therapy in inflammatory and degenerative diseases. Nature Reviews Drug Discovery. 2015;14:857-877.
9. Markiewski MM, Lambris JD. The role of complement in inflammatory diseases from behind the scenes into the spotlight. Am J Pathol. 2007;171(3):715-727.